The six projects constituting this application deal with interrelated aspects of the pulmonary circulation in health and disease. Project 1 considers the mechanical problem of blood flow from the right ventricle to the left atrium, and proposes to unravel the mechanisms which the organism uses to readjust the impedance characteristics of the lung vasculature in disease, to minimize cardiac work. The next two projects deal with response of the lung vascular bed to abnormal gas tensions. More particularly, Project 2 studies the development of the hypoxic response during embryonic life and the time relationship between inception of that reflex and other regulating mechanisms, while Project 3 is designed to elucidate the influence of the general conditions of the organism (e.g., hypoxia, acid-base imbalance) on the local response to abnormal gas composition. Project 4 carries this study one step further by addressing itself to the physiology of vascular smooth muscle and factors affecting its contraction. In Project 5, we propose to determine the effects of various characteristics of the vascular system as they affect the main function of the lung, gas exchange. Finally, Project 6 concentrates on the effects of injury on the pulmonary endothelium, and provides an anatomical basis for some of the functional studies.